Abstract IA04: The carcinogenic potential of bacterial biofilms

Abstract

Abstract The colonic microbiome is hypothesized to contribute to CRC pathogenesis and to potentially act as an initiator of colon oncogenesis, in part via induction of specific mucosal pro-carcinogenic immune responses. Both we and others have presented data from experimental models implicating specific bacteria in colon carcinogenesis. Enterotoxigenic Bacteriodes fragilis (ETBF), Escherichia coli containing the pks island [E. coli (pks)] and Fusobacterium nucleatum represent colon carcinogenic bacteria strongly implicated to date in both experimental models and human disease. To further address the links between the microbiota and human colon cancer, we are prospectively studying the microbial associations of human CRC together with parameters of mucosal immunity. Paired surgical CRC samples and normal colon mucosa are studied along with colon biopsies (right and left) of healthy controls undergoing screening colonoscopy. We have presented data demonstrating that sporadic colon tumors located proximal to the hepatic flexure are characterized by invasive polymicrobial biofilms that extend to normal colon tissue far distant from the tumor. In contrast, biofilm formation is infrequent in colon tumors distal to the hepatic flexure and in the mucosa of colonoscopy controls. Biofilm formation in the human colon is associated with changes in E-cadherin, IL-6 induction, activation of pStat3, colonic epithelial cell proliferation as well as polyamine metabolism. These data suggest biofilm formation promotes pro-carcinogenic immune and epithelial signaling in the human colon. We have further tested our hypothesis that biofilm formation contributes to colon carcinogenesis by examining surgically-removed colons from individuals with Familial Adenomatous Polyposis (FAP) who are destined, as Apc+/- heterozygotes, to develop colon cancer. In contrast to sporadic CRC, early stage FAP patients display patchy biofilm formation throughout the colon and the bacterial composition of FAP-associated colon biofilms differs. Murine studies support synergistic induction of colon tumor formation by select biofilm bacterial members. Together our studies provide additional support for the hypothesis that the microbiota and, specifically, biofilms are an environmental contributor to CRC pathogenesis. Citation Format: Cynthia L. Sears. The carcinogenic potential of bacterial biofilms. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA04.